Affinity-independent memory B cell origin of the early antibody-secreting cell response in naive individuals upon SARS-CoV-2 vaccination.

Memory B cells (MBCs) formed over the individual's lifetime constitute nearly half of the circulating B cell repertoire in humans. These pre-existing MBCs dominate recall responses to their cognate antigens, but how they respond to recognition of novel antigens is not well understood. Here, we tracked the origin and followed the differentiation paths of MBCs in the early anti-spike (S) response to mRNA vaccination in SARS-CoV-2-naive individuals on single-cell and monoclonal antibody levels.

Serine enrichment in tumors promotes regulatory T cell accumulation through sphinganine-mediated regulation of c-Fos.

CD4 regulatory T (T) cells accumulate in the tumor microenvironment (TME) and suppress the immune system. Whether and how metabolite availability in the TME influences T cell differentiation is not understood. Here, we measured 630 metabolites in the TME and found that serine and palmitic acid, substrates required for the synthesis of sphingolipids, were enriched.

Mast cells link immune sensing to antigen-avoidance behaviour.

The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance.

Usp22 is an intracellular regulator of systemic emergency hematopoiesis.

Emergency hematopoiesis is a concerted response aimed toward enhanced protection from infection, involving multiple cell types and developmental stages across the immune system. Despite its importance, the underlying molecular regulation remains poorly understood. The deubiquitinase USP22 regulates the levels of monoubiquitinated histone H2B (H2Bub1), which is associated with activation of interferon responses upon viral infection.

Toward the dissection of hematopoietic stem cell fates and their determinants.

Hematopoietic stem cell (HSC) functions have long been difficult to study under physiological conditions. Recently, genetic in vivo approaches have been developed for lineage tracing of differentiating progeny emerging from HSC over time (output), and for high-resolution, endogenous barcoding to uncover the lineages that HSC contribute to (fate). Such fate measurements have in principle led to the recognition of three major fate groups of HSC: multilineage, myelo-erythroid-restricted, and inactive, that is, no or no known progeny, in addition to a minor group of megakaryocyte-restricted HSC.

Resolving Fates and Single-Cell Transcriptomes of Hematopoietic Stem Cell Clones by PolyloxExpress Barcoding.

Lineage tracing reveals hematopoietic stem cell (HSC) fates, while single-cell RNA sequencing identifies snapshots of HSC transcriptomes. To obtain information on fate plus transcriptome in the same cell, we developed the PolyloxExpress allele, enabling Cre-recombinase-dependent RNA barcoding in situ. Linking fates to single HSC transcriptomes provided the information required to identify transcriptional signatures of HSC fates, which were not apparent in single-HSC transcriptomes alone.